Determination of GP88 (progranulin) expression in breast tumor biopsies improves the risk predictive value of the Nottingham Prognostic Index.
Determination of GP88 (progranulin) expression in breast tumor biopsies improves the risk predictive value of the Nottingham Prognostic Index.
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DOI：
10.1186/s13000-016-0520-4
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发表时间：
2016-08-08
影响因子：
2.6
通讯作者：
Yue B
中科院分区：
文献类型：
--
作者：
Serrero G;Hawkins DM;Bejarano PA;Ioffe O;Tkaczuk KR;Elliott RE;Head JF;Phillips J;Godwin AK;Weaver J;Hicks D;Yue B
诺丁汉预后指数 (NPI) 结合了淋巴结状态、肿瘤大小和组织学分级的数值，用于护理标准，为原发性乳腺癌患者的术后生存提供预测价值信息。通过测试其他生物标志物表达和形态特征（如血管侵犯）的包含情况，已尝试提高 NPI 算法的性能。在本研究中，我们研究了已知在乳腺癌中过度表达的自分泌生长和生存因子 GP88（颗粒体蛋白前体）的表达是否会提高 NPI 的预测价值。我们通过免疫组织化学 (IHC) 检查了 508 例雌激素受体阳性浸润性导管癌患者中 GP88 的表达，这些患者的临床结果已知，且 NPI 已确定。 GP88 IHC表达由两名委员会认证的病理学家进行评分，并分为GP88<3+（0、1+、2+）和GP88 = 3+两个评分组。然后通过 Kaplan-Meier 分析、Cox 比例风险 (CPH) 比和 Pearson X2 检验检查 GP88 评分、NPI 和无病 (DFS) 或总生存 (OS) 结果之间的相关性。按 NPI 评分（<3.4、3.4–5.4、>5.4）和 GP88 表达分类的病例的 Kaplan-Meier 生存图显示，对于同一 NPI 亚组内的患者，具有高 GP88 表达（GP88 IHC 评分为 3+）的肿瘤患者的 DFS 比具有低 GP88 表达（GP88 IHC 评分 <3+）的肿瘤患者差。根据 NPI 进行调整后，高 GP88 评分与复发显着相关，风险比为 3.30（95% CI 2.12 至 5.14）。数据表明，在诊断早期乳腺癌患者时测定 GP88 肿瘤表达可以为单独 NPI 提供的生存信息提供额外的生存信息，因此可能有助于诊断乳腺癌患者的风险管理。
The Nottingham Prognostic Index (NPI), which combines numerical values for nodal status, tumor size and histological grade, is used in the standard of care to provide predictive value information on post-surgery survival for patients with primary breast cancer. Attempts to improve the performance of the NPI algorithm have been carried out by testing the inclusion of other biomarker expression and morphological features such as vascular invasion. In the present study, we investigated whether expression of the autocrine growth and survival factor GP88 (progranulin), known to be overexpressed in breast cancer, would improve NPI’s predictive value. We examined by immunohistochemistry (IHC) the GP88 expression in 508 cases of estrogen receptor positive invasive ductal carcinoma with known clinical outcomes and for which NPI had been determined. GP88 IHC expression was scored by two board certified pathologists and classified into two score groups of GP88 <3+ (0, 1+, 2+) and GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) or overall survival (OS) outcomes was then examined by Kaplan-Meier analysis, Cox proportional Hazard (CPH) ratio and Pearson’s X2 test. Kaplan-Meier survival graphs of cases categorized by their NPI scores (<3.4, 3.4–5.4, >5.4) and GP88 expression showed that for patients within the same NPI subgroup, patients having tumors with a high GP88 expression (GP88 IHC score of 3+) had a worse DFS than patients with tumors that had a low GP88 expression (GP88 IHC score <3+). When adjusted for NPI, high GP88 score was significantly associated with recurrence with a hazard ratio of 3.30 (95 % CI 2.12 to 5.14). The data suggest that the determination of GP88 tumor expression at time of diagnosis for early stage breast cancer patients can provide additional survival information to that provided by NPI alone and thus may be useful for risk management of patients diagnosed with breast cancer.